Investigators of the Duke CRC/PE propose to continue and expand activities developed during the first five years of this award. The primary goal of the Duke Center is to define and validate a limited number of depressive subtypes in late life that are clinically relevant and prime for further study because of recent advances in neurosciences, psychometric assessment, nosology, epidemiology, biostatistics, as well as biologic approaches to therapy. Specifically, the Duke Center will continue to recruit approximately 160 subjects per year equally distributed between young/middle-aged (30-59) and elderly (60+) depressed inpatients and outpatients. Each subject recruited will undergo a baseline evaluation, including evaluation of both Axis I and Axis II DSM-III-R diagnoses, cognitive functioning, severity of depressive symptoms, baseline laboratory data, physical and social functioning. Subjects will be allocated, as appropriate, to three ongoing CRC Programs: 1) the Biological Markers Program; 2) the Brain MRI Program; and 3) the Effects of ECT in the Elderly Program. Subjects will also be allocated to four new pilot projects: 1) the Social Factors and Outcome of Major Depression Study; 2) the Natural History of Late Life Depression Study; 3) the Sleep Disorders and Depression Pilot; and 4) the Family History of Depression and Dementia Pilot. CRC investigators will pursue, among others, the following findings from previous CRC studies during the next five years to achieve the goal of subtyping depressive disorders: 1) nosological investigations that indicate longitudinal data and data on social functioning (improve prognosis); 2) the relevance of the receptor that bind tritiated imipramine (as a marker of depressive sub-types in the elderly; 3) the importance of family history in defining subtypes of late life depression (especially when depression is comorbid with dementia); 4) the relationship between late life depression and structural brain abnormalities, and 5) the effectiveness and side effects of ECT in the elderly.